Characteristics of extracellular ATP-stimulated norepinephrine (NE) secretion were investigated by the batch method in relation to membrane current measured with the whole cell voltage-clamp technique. Extracellular ATP stimulated [3H]NE secretion from PC12 cells in a concentration range from 10 μM to 1 mM. The maximal effect of ATP was about 5 times larger than that of nicotine. ATP-stimulated secretion was extracellular Ca-dependent, but it was not inhibited by the Ca-channel blockers, cadmium (300 μM) or nicardipine (10 μM). Extracellular ATP activated an inward current in PC12 cells and the peak amplitude of the current was about 5 times larger than that activated by nicotine. These findings suggest that extracellular ATP activates receptor-operated channels and causes NE secretion.
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